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Potency Evaluation of a Formulated Drug Product Containing 150-kd Botulinum Neurotoxin Type A

Hunt, Terrence BS; Clarke, Kenneth PhD

Clinical Neuropharmacology:
doi: 10.1097/WNF.0b013e3181692735
Original Articles
Abstract

Objective: To assess the potency of a formulated drug product containing 150-kd botulinum toxin type A (BoNT/A) as the active pharmaceutical ingredient.

Methods: Potencies of 3 unexpired lots of a commercially available BoNT/A drug product, reportedly devoid of complexing proteins (Xeomin), were determined using an approved in-house potency bioassay by injecting mice intraperitoneally and recording percent-mortality across dilutions. For each test session, duplicate sets of dilutions were performed for each lot alongside a 900-kd BoNT/A (BOTOX) potency reference standard. A relative potency for each 150-kd BoNT/A preparation was determined using this potency reference standard. A standard normalized potency estimate for each lot of 150-kd BoNT/A was calculated by multiplying the relative potency by the nominal value for the reference standard. The average potency for each 150-kd BoNT/A lot was calculated using a weighted combination of assay results and compared against the labeled potency of 100 U per vial. Similar follow-on testing was performed 1 year later to assess stability.

Results: The average potencies for the 3 lots of 150-kd BoNT/A product were 69 (95% confidence interval [CI], 65-73), 75 (95% CI, 70-80), and 78 (95% CI, 70-87) U per vial. Follow-on testing produced even lower potency results for all 3 lots.

Conclusions: The potency of the drug product containing 150-kd BoNT/A (Xeomin) measured substantially lower than the labeled 100 U per vial when tested in a potency assay approved for release testing of an established drug product containing 900-kd BoNT/A (BOTOX).

Author Information

Department of Biological Sciences, Allergan, Inc, Irvine, CA.

Address correspondence and reprint requests to Terrence Hunt, BS, Neurotoxin Research Program Biological Sciences, R&D, Allergan, Inc, 2525 Dupont Drive RD3-3B, Irvine, CA 92612-1599; E-mail: hunt_terrence@allergan.com

This study was supported by Allergan, Inc.

© 2009 Lippincott Williams & Wilkins, Inc.